Identification

Name
Varenicline
Accession Number
DB01273
Type
Small Molecule
Groups
Approved, Investigational
Description

Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors.

On March 9, 2015, the U.S. Food and Drug Administration warned that Varenicline, in the form of Pfizer Inc's quit-smoking drug, Chantix, has been associated with seizures and that some patients who drink while taking the drug may become aggressive or black out. Pfizer is conducting an additional safety study of the drug, results of which are expected in late 2015. The FDA said it is keeping the black box in place at least until the results of the trial are announced.

Structure
Thumb
Synonyms
  • vareniclina
External IDs
CP-526,555 / CP-526555
Product Ingredients
IngredientUNIICASInChI Key
Varenicline tartrate82269ASB48375815-87-5TWYFGYXQSYOKLK-LREBCSMRSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ChampixTablet, film coated0.5 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1.0 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1.0 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet0.5 mgOralPfizer2007-04-11Not applicableCanada
ChampixTablet, film coated1 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated0.5 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
ChampixTablet, film coated1.0 mgOralPfizer Europe Ma Eeig2006-09-26Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-vareniclineTablet0.5 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-vareniclineTablet1 mgOralApotex CorporationNot applicableNot applicableCanada
Gd-vareniclineTablet0.5 mgOralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
Gd-vareniclineTablet1.0 mgOralGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
PMS-vareniclineTablet0.5 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-vareniclineTablet1 mgOralPharmascience IncNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ChampixVarenicline (0.5 mg) + Varenicline (1 mg)Kit; TabletOralPfizer2007-10-02Not applicableCanada
ChampixVarenicline (0.5 mg) + Varenicline (1 mg)Kit; TabletOralPfizer2007-10-02Not applicableCanada
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitRebel Distributors2006-05-10Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitLake Erie Medical Dba Quality Care Produts Llc2006-05-102015-06-30Us
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitU.S. Pharmaceuticals2006-05-10Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitPfizer Laboratories Div Pfizer Inc.2006-05-10Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitProficient Rx LP2006-05-10Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitPhysicians Total Care, Inc.2006-09-01Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitRebel Distributors2006-05-10Not applicableUs
ChantixVarenicline tartrate (0.5 mg/1) + Varenicline tartrate (1 mg/1)KitLake Erie Medical Dba Quality Care Produts Llc2006-05-102015-06-30Us
Categories
UNII
W6HS99O8ZO
CAS number
249296-44-4
Weight
Average: 211.2624
Monoisotopic: 211.110947431
Chemical Formula
C13H13N3
InChI Key
JQSHBVHOMNKWFT-DTORHVGOSA-N
InChI
InChI=1S/C13H13N3/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1/h1-2,4-5,8-9,14H,3,6-7H2/t8-,9+
IUPAC Name
(1R,12S)-5,8,14-triazatetracyclo[10.3.1.0²,¹¹.0⁴,⁹]hexadeca-2,4,6,8,10-pentaene
SMILES
[H][C@]12C[C@]([H])(CNC1)C1=CC3=NC=CN=C3C=C21

Pharmacology

Indication

For use as an aid in smoking cessation.

Associated Therapies
Pharmacodynamics

Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.

Mechanism of action

Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-4
partial agonist
Human
UNeuronal acetylcholine receptor subunit alpha-7
agonist
Human
UNeuronal acetylcholine receptor subunit alpha-3
partial agonist
Human
UNeuronal acetylcholine receptor subunit alpha-6
partial agonist
Human
UNeuronal acetylcholine receptor subunit beta-2
partial agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Less than 20%.

Metabolism

Metabolism is limited (<10%). Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.

Route of elimination

Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2.

Half life

The elimination half-life of varenicline is approximately 24 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when 1,10-Phenanthroline is combined with Varenicline.
AbacavirAbacavir may decrease the excretion rate of Varenicline which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Varenicline which could result in a higher serum level.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Varenicline.
AceclofenacAceclofenac may decrease the excretion rate of Varenicline which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Varenicline which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Varenicline which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Varenicline which could result in a higher serum level.
AclidiniumVarenicline may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineVarenicline may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Vinod Kumar Kansal, Suhail Ahmad, Amit Gupta, "PROCESSES FOR THE PREPARATION OF VARENICLINE AND INTERMEDIATES THEREOF." U.S. Patent US20090318695, issued December 24, 2009.

US20090318695
General References
  1. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. [PubMed:16820547]
  2. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. [PubMed:16766716]
  3. Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW: Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121-30. Epub 2005 Oct 12. [PubMed:16221753]
  4. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. [PubMed:15887955]
  5. Kuehn BM: FDA speeds smoking cessation drug review. JAMA. 2006 Feb 8;295(6):614. [PubMed:16467225]
External Links
Human Metabolome Database
HMDB0015398
PubChem Compound
5310966
PubChem Substance
46505502
ChemSpider
4470510
BindingDB
221048
ChEBI
84500
ChEMBL
CHEMBL1076903
Therapeutic Targets Database
DAP001535
PharmGKB
PA164781343
HET
QMR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Varenicline
ATC Codes
N07BA03 — Varenicline
AHFS Codes
  • 12:92.00 — Miscellaneous Autonomic Drugs
PDB Entries
4afg / 4aft / 5ain
FDA label
Download (334 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingPreventionCessation, Smoking / Tobacco Dependence1
0Active Not RecruitingTreatmentCessation, Smoking / Head and Neck Carcinoma1
0CompletedTreatmentAlcohol Use Disorders (AUD) / Smoking, Cigarette1
0RecruitingOtherCessation, Smoking / Smoking / Smoking, Cigarette / Tobacco Smoking Behavior1
0RecruitingPreventionCurrent Smokers / Head and Neck Squamous Cell Carcinoma (HNSCC) / Hypopharyngeal Squamous Cell Carcinoma / Laryngeal Squamous Cell Carcinoma / Nasopharyngeal Carcinoma / Oral Cavity Squamous Cell Carcinoma / Oropharyngeal Squamous Cell Carcinoma1
0TerminatedTreatmentCessation, Smoking1
1CompletedNot AvailableCessation, Smoking1
1CompletedNot AvailableHealthy Volunteers / Non-Smoking1
1CompletedNot AvailableMethamphetamine Abuse / Methamphetamine Dependence / Substance Abuse1
1CompletedBasic ScienceTobacco Use Disorders1
1CompletedTreatmentAdditional, Effective Methods to Stop Smoking1
1CompletedTreatmentAmphetamine Addiction / Crystal Meth Addiction / Methamphetamine Addiction1
1CompletedTreatmentCessation, Smoking2
1CompletedTreatmentOpioid Dependence / Pain, Chronic1
1CompletedTreatmentSmoking1
1CompletedTreatmentSmoking, Cigarette1
1Enrolling by InvitationBasic ScienceCognitive Function / Dopamine D2/3 Receptor Availability / Methamphetamine Abuse1
1RecruitingTreatmentAlcohol Consumption / Heavy Drinking / Nicotine Dependence / Smoking, Cigarette1
1WithdrawnNot AvailableMethamphetamine Abuse / Methamphetamine Dependence / Substance Abuse1
1WithdrawnOtherNicotine Dependence1
1WithdrawnOtherSubstance, Addiction1
1, 2CompletedTreatmentAlcohol Drinking1
1, 2CompletedTreatmentAlcohol Use Disorder (AUD)1
1, 2CompletedTreatmentLung Cancers1
1, 2CompletedTreatmentNicotine Dependence / Smoking1
1, 2CompletedTreatmentTobacco Use Disorders / Weight gain therapy1
1, 2WithdrawnNot AvailableNicotine Dependence1
2Active Not RecruitingTreatmentDependence, Cocaine1
2CompletedNot AvailableSchizophrenic Disorders1
2CompletedTreatmentAlcohol Abuse / Alcohol Dependence / Alcohol Drinking / Smoking1
2CompletedTreatmentAlcohol Dependence3
2CompletedTreatmentAlcohol Dependence / Dependence, Cocaine1
2CompletedTreatmentAlcohol Drinking1
2CompletedTreatmentAlcohol Reactivity1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentCessation, Smoking6
2CompletedTreatmentCessation, Smoking / Schizophrenic Disorders1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentHeavy Drinking / Nicotine Dependence / Smoking1
2CompletedTreatmentMethamphetamine Abuse / Methamphetamine Dependence / Substance Abuse2
2CompletedTreatmentNicotine Dependence4
2CompletedTreatmentNicotine Dependence / Post Traumatic Stress Disorder (PTSD) / Smoking, Cigarette / Tobacco Use Disorders1
2CompletedTreatmentNicotine Dependence / Tobacco Use Cessation / Tobacco Use Disorders1
2CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
2CompletedTreatmentSchizophrenic Disorders / Smoking, Cigarette1
2CompletedTreatmentSmoking2
2CompletedTreatmentSmoking Behavior / Smoking Lapse Behavior / Smoking Relapse Behavior1
2CompletedTreatmentSmoking Lapse Behavior1
2CompletedTreatmentSmoking, Cigarette1
2CompletedTreatmentSpinocerebellar Ataxia Type 31
2CompletedTreatmentTobacco Dependence1
2CompletedTreatmentTobacco Use Disorders1
2Enrolling by InvitationTreatmentParkinson's Disease (PD)1
2Not Yet RecruitingBasic ScienceTobacco Dependence1
2Not Yet RecruitingTreatmentCessation, Smoking1
2RecruitingTreatmentAlcohol Use Disorder (AUD) / Nicotine Dependence1
2RecruitingTreatmentParkinson's Disease (PD)1
2RecruitingTreatmentSubstance Use Disorder (SUD)1
2TerminatedTreatmentBMI >30 kg/m2 / Smoking, Cigarette1
2Unknown StatusTreatmentAlcohol Dependence1
2Unknown StatusTreatmentSmoking1
2WithdrawnBasic ScienceVarenicline and the Blunting of Cocaine Cues1
2WithdrawnTreatmentCessation, Smoking1
2WithdrawnTreatmentDependence, Cocaine1
2WithdrawnTreatmentSchizophrenic Disorders1
2, 3Active Not RecruitingPreventionCessation, Smoking / Habits / Smoking1
2, 3Active Not RecruitingTreatmentCessation, Smoking / Tobacco Use Disorders1
2, 3Active Not RecruitingTreatmentTobacco Use Cessation1
2, 3CompletedPreventionTobacco Use Disorders1
2, 3CompletedTreatmentAlcohol Dependence / Smoking / Tobacco Dependence1
2, 3CompletedTreatmentNicotine Dependence / Nicotine Withdrawal1
2, 3CompletedTreatmentSmoking1
2, 3CompletedTreatmentTobacco Abstinence1
2, 3RecruitingTreatmentAlcohol Use / Human Immunodeficiency Virus (HIV) Infections / Smoking1
2, 3RecruitingTreatmentBMI >30 kg/m2 / Cessation, Smoking1
2, 3RecruitingTreatmentCessation, Smoking / Opioid Related Disorders1
2, 3TerminatedTreatmentFriedreich's Ataxia1
2, 3TerminatedTreatmentNicotine Dependence / Smoking, Cigarette1
2, 3Unknown StatusTreatmentTobacco Dependence1
3Active Not RecruitingTreatmentCessation, Smoking1
3Active Not RecruitingTreatmentCessation, Smoking / Human Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentNicotine Dependence2
3Active Not RecruitingTreatmentNicotine Dependence / Tobacco Use1
3CompletedNot AvailableCessation, Smoking1
3CompletedPreventionAcute Coronary Syndromes (ACS)1
3CompletedTreatmentAcute Exacerbation of Chronic Obstructive Pulmonary Disease / Chronic Obstructive Pulmonary Disease (COPD) / Smoking1
3CompletedTreatmentCessation, Smoking10
3CompletedTreatmentCessation, Smoking / Tobacco Dependence3
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tobacco Dependence1
3CompletedTreatmentNicotine Addiction1
3CompletedTreatmentNicotine Dependence4
3CompletedTreatmentSchizophrenic Disorders1
3RecruitingPreventionCessation, Smoking / Chronic Obstructive Pulmonary Disease (COPD)1
3RecruitingPreventionSmokers With Cancer1
3RecruitingSupportive CareLung, Carcinoma1
3RecruitingTreatmentCessation, Smoking1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Smoking1
3RecruitingTreatmentTobacco Smoking Behavior1
3TerminatedTreatmentAlcohol Dependence / Nicotine Dependence1
4Active Not RecruitingPreventionCessation, Smoking1
4Active Not RecruitingTreatmentCessation, Smoking1
4Active Not RecruitingTreatmentCessation, Smoking / Nicotine Dependence / Smoking1
4Active Not RecruitingTreatmentTobacco Use Cessation1
4CompletedNot AvailableCessation, Smoking3
4CompletedDiagnosticCessation, Smoking / Recurrences / Substance-Related Disorders1
4CompletedHealth Services ResearchCessation, Smoking1
4CompletedOtherCraving / Schizophrenic Disorders / Smoking1
4CompletedPreventionCerebrovascular Disorders / Cessation, Smoking1
4CompletedPreventionCessation, Smoking / Psychiatric Illness1
4CompletedPreventionCoronary Heart Disease (CHD)1
4CompletedScreeningNicotine Dependence1
4CompletedTreatmentAlcohol Abuse / Cessation, Smoking1
4CompletedTreatmentAsthma Bronchial1
4CompletedTreatmentAsthma Bronchial / Community Acquired Pneumonia (CAP) / Pulmonary Disease, Chronic Obstructive1
4CompletedTreatmentBipolar Disorder (BD) / Cessation, Smoking1
4CompletedTreatmentBipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenic Disorders / Smoking1
4CompletedTreatmentCessation, Smoking9
4CompletedTreatmentCessation, Smoking / Depression1
4CompletedTreatmentCessation, Smoking / Smoking / Tobacco Use Disorders1
4CompletedTreatmentNicotine Dependance / Schizophrenic Disorders / Tobacco Use Disorders / Tobocco Use Disorder1
4CompletedTreatmentNicotine Dependence1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
4CompletedTreatmentSchizophrenic Disorders / Smoking, Cigarette1
4CompletedTreatmentSmoking3
4CompletedTreatmentSmoking Addiction1
4CompletedTreatmentTobacco Use Cessation1
4Not Yet RecruitingTreatmentCessation, Smoking1
4Not Yet RecruitingTreatmentOpioid-use Disorder / Tobacco Use Disorders1
4Not Yet RecruitingTreatmentParkinsonism / Schizoaffective Disorders / Schizophrenic Disorders / Tardive Dyskinesia / Tobacco Smoking Behavior1
4RecruitingTreatmentAlcohol Drinking / Cessation, Smoking1
4RecruitingTreatmentCessation, Smoking1
4RecruitingTreatmentCessation, Smoking / Electronic Cigarette1
4RecruitingTreatmentCigarette Smokers / Tobacco Use Cessation / Tobacco Use Disorders1
4RecruitingTreatmentMajor Depressive Disorder (MDD) / Nicotine Dependence1
4RecruitingTreatmentMedication Adherence1
4RecruitingTreatmentNicotine Dependence1
4RecruitingTreatmentTobacco Dependence1
4TerminatedTreatmentAlcohol Dependence / Nicotine Dependence / Schizoaffective Disorders / Schizophrenic Disorders1
4TerminatedTreatmentAttention Deficit/Hyperactivity Disorder / Cessation, Smoking1
4TerminatedTreatmentMethadone Maintenance / Smoking, Cigarette1
4TerminatedTreatmentParkinson's Disease (PD)1
4Unknown StatusPreventionCessation, Smoking1
4Unknown StatusTreatmentCessation, Smoking / Substance-Related Disorders1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Smoking, Cigarette1
4Unknown StatusTreatmentSmoking1
4WithdrawnTreatmentAlcohol Consumption / Smoking, Cigarette1
4WithdrawnTreatmentPsychosis / Schizoaffective / Schizophrenic Disorders1
4WithdrawnTreatmentTobacco Use Disorders1
Not AvailableActive Not RecruitingNot AvailableCardiovascular Disease (CVD) / Cessation, Smoking / Depression / Feeling Anxious / Myocardial Infarction / Respiratory Diseases / Respiratory Illness1
Not AvailableActive Not RecruitingBasic ScienceSmoking, Cigarette1
Not AvailableCompletedNot AvailableCessation, Smoking6
Not AvailableCompletedNot AvailableMalformations1
Not AvailableCompletedNot AvailableTobacco Dependence1
Not AvailableCompletedBasic ScienceNicotine Dependence1
Not AvailableCompletedBasic ScienceSubstance Dependence1
Not AvailableCompletedHealth Services ResearchDependence, Cocaine / Nicotine Dependence1
Not AvailableCompletedOtherNicotine Dependence1
Not AvailableCompletedPreventionBladder Cancers / Cervical Cancers / Esophageal Cancers / Head and Neck Carcinoma / Leukemias / Liver Cancer / Lung Cancers / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach / Renal Cancers / Tobacco Use Disorders1
Not AvailableCompletedPreventionTobacco Use Disorders1
Not AvailableCompletedPreventionUnspecified Adult Solid Tumor, Protocol Specific1
Not AvailableCompletedSupportive CareSmoking1
Not AvailableCompletedTreatmentAlcohol Dependence / Tobacco Dependence1
Not AvailableCompletedTreatmentBipolar Disorder (BD) / Depression / Smoking1
Not AvailableCompletedTreatmentCessation, Smoking1
Not AvailableCompletedTreatmentCessation, Smoking / Diabetes Mellitus (DM)1
Not AvailableCompletedTreatmentCessation, Smoking / Health Behavior / Lifestyle-related Condition1
Not AvailableCompletedTreatmentCessation, Smoking / Medication Adherence1
Not AvailableCompletedTreatmentCessation, Smoking / Nicotine Dependence1
Not AvailableCompletedTreatmentCognition in Schizophrenia1
Not AvailableCompletedTreatmentDepressive Disorders / Smoking1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Smoking1
Not AvailableCompletedTreatmentNicotine Dependence4
Not AvailableCompletedTreatmentNicotine Dependence / Tobacco Use Disorders1
Not AvailableCompletedTreatmentPeriodontitis1
Not AvailableCompletedTreatmentSmokers1
Not AvailableCompletedTreatmentTobacco Use Cessation1
Not AvailableCompletedTreatmentTobacco Use Disorders1
Not AvailableEnrolling by InvitationNot AvailableCessation, Smoking1
Not AvailableEnrolling by InvitationTreatmentNicotine Dependence / Smokeless Tobacco1
Not AvailableNot Yet RecruitingHealth Services ResearchAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD) / Smoking1
Not AvailableRecruitingHealth Services ResearchNicotine Dependence, Cigarettes1
Not AvailableRecruitingTreatmentAcute Coronary Syndromes (ACS) / Cessation, Smoking1
Not AvailableRecruitingTreatmentCessation, Smoking / Genetic Predisposition1
Not AvailableRecruitingTreatmentCoronary Artery Disease1
Not AvailableTerminatedNot AvailableCancer, Breast / Tobacco Dependence1
Not AvailableTerminatedBasic ScienceSmoking1
Not AvailableWithdrawnTreatmentDepressive Disorders / Smoking1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Cardinal Health
  • Diversified Healthcare Services Inc.
  • Lake Erie Medical and Surgical Supply
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • US Pharmaceutical Group
Dosage forms
FormRouteStrength
TabletOral0.5 mg
TabletOral1 mg
Tablet, film coatedOral0.5 mg
Tablet, film coatedOral1 mg
Tablet, film coatedOral1.0 mg
Kit
Kit0.5 mg/1
Tablet, film coatedOral.5 mg/1
Tablet, film coatedOral0.5 mg/1
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral1.0 mg/1
Kit; tabletOral
TabletOral1.0 mg
Prices
Unit descriptionCostUnit
Chantix Continuing Month Pak 56 1 mg tablet Disp Pack148.5USD disp
Chantix Starting Month Pak 0.5 mg X 11, 1 mg X 42 Disp Pack148.5USD disp
Chantix 1 mg tablet2.61USD tablet
Chantix 0.5 mg tablet2.56USD tablet
Chantix 1 mg cont month pak2.56USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2525874No2007-11-272024-05-07Canada
CA2316921No2004-12-072018-11-13Canada
US6410550No2002-06-252020-05-10Us
US6890927No2005-05-102022-05-06Us
US7265119No2007-09-042022-08-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0877 mg/mLALOGPS
logP1.39ALOGPS
logP1.01ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)9.73ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.81 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity61.3 m3·mol-1ChemAxon
Polarizability23.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9969
Blood Brain Barrier+0.9908
Caco-2 permeable-0.5233
P-glycoprotein substrateSubstrate0.5458
P-glycoprotein inhibitor INon-inhibitor0.7453
P-glycoprotein inhibitor IINon-inhibitor0.9637
Renal organic cation transporterInhibitor0.5489
CYP450 2C9 substrateNon-substrate0.8933
CYP450 2D6 substrateNon-substrate0.6522
CYP450 3A4 substrateNon-substrate0.7428
CYP450 1A2 substrateNon-inhibitor0.507
CYP450 2C9 inhibitorNon-inhibitor0.881
CYP450 2D6 inhibitorInhibitor0.6251
CYP450 2C19 inhibitorNon-inhibitor0.8029
CYP450 3A4 inhibitorNon-inhibitor0.6589
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5453
Ames testNon AMES toxic0.7128
CarcinogenicityNon-carcinogens0.9592
BiodegradationNot ready biodegradable0.9906
Rat acute toxicity2.5914 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9382
hERG inhibition (predictor II)Inhibitor0.5497
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
Alternative Parents
Quinoxalines / Indanes / Azepines / Aralkylamines / Pyrazines / Piperidines / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds
show 1 more
Substituents
Benzazepine / Diazanaphthalene / Quinoxaline / Indane / Azepine / Aralkylamine / Piperidine / Benzenoid / Pyrazine / Heteroaromatic compound
show 9 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterotetracyclic compound, secondary amino compound, bridged compound (CHEBI:84500)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Nakamura M, Oshima A, Fujimoto Y, Maruyama N, Ishibashi T, Reeves KR: Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther. 2007 Jun;29(6):1040-56. [PubMed:17692720]
  2. McColl SL, Burstein AH, Reeves KR, Billing CB Jr, Stolar M, Sellers EM: Human abuse liability of the smoking cessation drug varenicline in smokers and nonsmokers. Clin Pharmacol Ther. 2008 Apr;83(4):607-14. doi: 10.1038/sj.clpt.6100510. Epub 2008 Feb 20. [PubMed:18288085]
  3. Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE: Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. Trends Pharmacol Sci. 2007 Jul;28(7):316-25. Epub 2007 Jun 18. [PubMed:17573127]
  4. Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12518-23. Epub 2007 Jul 11. [PubMed:17626178]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. [PubMed:16766716]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA3
Uniprot ID
P32297
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-3
Molecular Weight
57479.54 Da
References
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. [PubMed:16766716]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Acetylcholine-activated cation-selective channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA6
Uniprot ID
Q15825
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-6
Molecular Weight
56897.745 Da
References
  1. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. [PubMed:16766716]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNB2
Uniprot ID
P17787
Uniprot Name
Neuronal acetylcholine receptor subunit beta-2
Molecular Weight
57018.575 Da
References
  1. Niaura R, Jones C, Kirkpatrick P: Varenicline. Nat Rev Drug Discov. 2006 Jul;5(7):537-8. [PubMed:16883648]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
A study demonstrated that varenicline, excreted by the kidney predominantly without undergoing metabolism, serves as an OCT2 substrate in vitro, and, at a much higher concentration, as an OCT2 inhibitor.
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Feng B, Obach RS, Burstein AH, Clark DJ, de Morais SM, Faessel HM: Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study. Clin Pharmacol Ther. 2008 Apr;83(4):567-76. doi: 10.1038/sj.clpt.6100405. Epub 2007 Oct 31. [PubMed:17971819]
  2. Bergen AW, Javitz HS, Krasnow R, Michel M, Nishita D, Conti DV, Edlund CK, Kwok PY, McClure JB, Kim RB, Hall SM, Tyndale RF, Baker TB, Benowitz NL, Swan GE: Organic cation transporter variation and response to smoking cessation therapies. Nicotine Tob Res. 2014 Dec;16(12):1638-46. doi: 10.1093/ntr/ntu161. Epub 2014 Aug 20. [PubMed:25143296]

Drug created on May 16, 2007 14:24 / Updated on December 12, 2018 07:14